ArticleJournal of the American Chemical Society2013
A dynamic structural model of expanded RNA CAG repeats: a refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Longer Is Not Always Better: Effects of Equilibration Length on Umbrella Sampling Estimations for RNA Hairpin Folding Stabilities.bioRxiv : the preprint server for biology · 2026Article
- Nucleotide-Specific RNA Conformations and Dynamics as Precursors to Ribonucleoprotein Condensates.Journal of the American Chemical Society · 2025Article
- Experimental and computational investigations of RNA duplexes containing N7-regioisomers of adenosine and LNA-adenosine.Nucleic acids research · 2025Article
- Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.Biomolecules · 2024Review
- NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- Dynamic docking of small molecules targeting RNA CUG repeats causing myotonic dystrophy type 1.Biophysical journal · 2023Article
- Molecular insights into the interaction of CAG trinucleotide RNA repeats with nucleolin and its implication in polyglutamine diseases.Nucleic acids research · 2022Article
- Evaluating Geometric Definitions of Stacking for RNA Dinucleoside Monophosphates Using Molecular Mechanics Calculations.Journal of chemical theory and computation · 2022Article
- Computational Investigation of Bending Properties of RNA AUUCU, CCUG, CAG, and CUG Repeat Expansions Associated With Neuromuscular Disorders.Frontiers in molecular biosciences · 2022Article
- Spontaneous and frequent conformational dynamics induced by A…A mismatch in d(CAA)·d(TAG) duplex.Scientific reports · 2021Article
- Molecular conformations and dynamics of nucleotide repeats associated with neurodegenerative diseases: double helices and CAG hairpin loops.Computational and structural biotechnology journal · 2021Review
- Atypical structures of GAA/TTC trinucleotide repeats underlying Friedreich's ataxia: DNA triplexes and RNA/DNA hybrids.Nucleic acids research · 2020Article
- Dynamics of strand slippage in DNA hairpins formed by CAG repeats: roles of sequence parity and trinucleotide interrupts.Nucleic acids research · 2020Article
- Exploring the Potential of Small Molecule-Based Therapeutic Approaches for Targeting Trinucleotide Repeat Disorders.Molecular neurobiology · 2020Review
- Discovery of a potent small molecule inhibiting Huntington's disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein.Scientific reports · 2019Article
- Computational Investigation of RNA A-Bulges Related to the Microtubule-Associated Protein Tau Causing Frontotemporal Dementia and Parkinsonism.The journal of physical chemistry. B · 2019Article
- Principles for targeting RNA with drug-like small molecules.Nature reviews. Drug discovery · 2018Review
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.Biochemistry · 2018Article
- A B-Z junction induced by an A … A mismatch in GAC repeats in the gene for cartilage oligomeric matrix protein promotes binding with the hZαThe Journal of biological chemistry · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded CAG repeats can cause Huntington's and other disease through translation of toxic proteins. Herein, a crystal structure of r[5'UUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that shows both anti-anti and syn-anti orientations for 1 × 1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using AMBER force field in explicit solvent were run for over 500 ns on the model systems r(5'GCGCAGCGC)2 (MS1) and r(5'CCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti ↔ anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, an explicit solvent MD simulation over 800 ns was run on r[5'GGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1 × 1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and to develop small molecules that target RNA dynamic ensembles.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.